Catheters are commonly utilized especially by physicians and other health care personnel for various purposes, such as the long and short term intravenous delivery (infusion) and withdrawal of fluids, such as urine, Dialysis catheters, as well as blood and blood products for treatment and monitoring of the patient. Examples of catheters include urinary catheters, suction catheters, dialysis catheters, venous catheters, Swan-Ganz catheters, double and triple lumen central catheters, arterial catheters, arterial line monitoring catheters, to name but a few.
The widespread use of respiratory catheters, venous and or arterial catheters, urological catheters, and dialysis catheters has resulted in dangerous infections owing to the adherence and colonization of pathogens on the catheter surface. Moreover, colonized catheters may produce a reservoir of antimicrobial resistant microorganisms. Catheter-associated urinary tract infections are now the most common type of hospital acquired infections. Catheter-related bloodstream and respiratory infections are also very common and often result in morbidity. Antimicrobial catheters currently on the market have been shown to offer some degree of protection against dangerous microbes. These catheters use various active agents such as ionic silver, chlorhexidine and antibiotics. However, commercially available antimicrobial catheters have considerable drawbacks including a narrow range of antibacterial activity, little to no delivery controls and the potential to cause undesirable side effects when drug-based coatings such as ionic silver, chlorhexidine and antibiotics are used. Silver coatings, in particular have limited antibacterial effectiveness. Furthermore, development of bacterial resistance against drug based active agents from microbial mutations is well-known, rendering them ineffective.
Iodine is a well-known broad spectrum antimicrobial agent that has bactericidal, fungicidal and virucidal properties which has been used for over centuries as an antiseptic. When iodine reacts with aqueous solutions, free iodine, which provides the germicidal effect, is released. The control of the free iodine is dependent on the acidity of the coating as exemplified herein. Therefore, the pH range of the coating will determine whether the iodine is available for antimicrobial effectiveness. While generally inhibiting infective germs over the short term, the biocidal effectiveness of iodine is dependent on, inter alia, how long the infective agent is exposed to the iodine in the pH modified coating.
To increase the effectiveness of iodine, it is normally combined with a solubilizing agent or other carrier to form an iodophor. Such iodophors, in effect, provide a reservoir of iodine from which small amounts of free iodine in aqueous solution are released over a period of time. These iodophors formulated for example, as a solution, soap, cream or paste, are then topically applied to that area of a patient's body which is desired to be treated. Perhaps the best known of these iodophors is povidone-iodine solution in liquid form, in which iodine in the form of triiodide is complexed with the polymer polyvinylpyrrolidone. An example of such an application can be found by reference to U.S. Pat. No. 4,010,259.
It has also been disclosed in U.S. Pat. No. 4,381,380 issued to Le Veen et al, to provide cross-linked thermoplastic polyurethane articles, such as catheters, into which iodine (12) has been complexed for antibacterial use. While being useful for their purpose, such cross-linked thermoplastics cannot be utilized for coatings nor do they provide the same level of antibacterial protection. The encapsulation of the iodophor in polyurethanes is problematic in that the iodine cannot be released and is therefore not available for delivery in a controlled manner. Stated differently, the iodine (12) is imbedded within the polymer and is not available to react as an effective antimicrobial. A particular problem often faced with antimicrobial coated elastomeric catheters is that the biocidal material (volatile 12) may leach from the surface of the elastomeric product. Hence, the antimicrobial efficacy is significantly reduced over time. Moreover, such leaching may create significant problems, particularly when the elastomeric products are used in medical applications, for example, when proteins are present with 12 in latex or in elastomeric products with double bonds (imparting elastic deformation).
Another problem comes when the antimicrobial agent is directly incorporated into the underlying elastomeric material. While this can reduce leaching of iodine located on the surface of the elastomeric product, it also necessitates a relatively large amount of iodine be incorporated in order to exert a significant toxic effect on a broad spectrum of pathogens. The use of polymer coatings to incorporate iodine has the effect of trapping the iodine such that there is also a need for relatively large amounts of iodine to be incorporated in order to exert a significant toxic effect.
The present device has the ability to apply iodine in the form of polyiodides in a coating process which incorporates the antimicrobial agent only into the relatively thin outer coating layer that nonetheless provides for a steady release of iodine solely at the surface of the device.
The present device provides for a catheter which has a thermoset uncross-linked polymer coating that has iodine either complexed therein for quick and relative immediate release of the iodine and/or matrixed therein for sustained release of the iodine on the surface coating of said catheter.
Thus, it can be seen that there remains a need for catheters that are solvent coatable with a polymeric dispersion or solution that have iodine complexed and/or matrixed therein, so as to provide for immediate and/or sustained release of the iodine for inhibiting microbial growth, that is commonly associated with the use of such catheters.
Elastomeric materials have proven to be very valuable in many healthcare and medical applications. Several types of elastomeric polymers have properties which are ideal for such applications. For instance, materials such as latex, silicone and polyvinyl demonstrates a combination of softness, high tensile strength and excellent film-forming properties.
Hence, there is a need to develop new antimicrobial contact kill type products, where such catheters are effective against all currently known microorganisms, are nontoxic and are inexpensive to manufacture.
Polyiodide resins have proven to be as much as 1,000,000 times more effective than an iodine (12) molecule alone. A large number of chemical, biochemical, and physiological studies have proven that the iodine added to microorganisms is irreversibly bound. This has the effect of devitalizing the microorganisms by damaging cellular proteins, lipids, enzymes, oxidation of sulfhydryl groups and other chemical pathways.
Microorganisms carry a negative electrical potential energy on their surface when damp with water. The polyiodide resin carries a positive electrical potential charge. The microorganisms with their negative electrical potential are naturally drawn to the iodinated resin particles with their positive electrical potential charge, thus ensuring contact kill. The iodinated resin releases the correct lethal dose of nascent iodine in less than 3 seconds at a body temperature 98.6° F. or 36.9° C.
The ion-exchange resin bead or particle is chemically bonded homogeneously with polyiodide of uniform composition throughout its interior. As nascent iodine is consumed more is continuously fed to the surface from the interior of the resin bead or particle.
The unique release on demand feature of polyiodide resin can be demonstrated by adding resin beads to the well of a depression microscope slide with a suspension of the highly motile ciliate Tetrahymena pyriformis. When observed microscopically, individual cells maintain their motion while swimming in a solution with 2 ppm of iodine residual. However after a collision with a resin bead, their activity dramatically slows and within seconds stops altogether.
Bacteria, viruses, yeast, fungi, and protozoa are not able to develop resistance to iodine even after a period of prolonged exposure to polyiodinated resins. It is not expected that emerging new microbial organisms will develop resistance to iodine, as historically there has been no development of resistance to iodine, as well as polyiodinated resin.